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An immunohistochemical assessment of cathepsin D in gastric carcinoma
Author(s) -
Allgayer Heike,
Babic Rudolf,
Grützner Klaus Uwe,
Beyer Bianca C. M.,
Tarabichi Anwar,
Schildberg Friedrich Wilhelm,
Heiss Markus Maria
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19970715)80:2<179::aid-cncr2>3.0.co;2-p
Subject(s) - medicine , cathepsin d , oncology , hazard ratio , gastroenterology , carcinoma , cathepsin , proportional hazards model , survival analysis , cancer , pathology , confidence interval , biology , biochemistry , enzyme
BACKGROUND In the context of tumor‐associated proteolysis, the prognostic value of cathepsin D in breast carcinoma has been studied but its role is controversial in relation to gastrointestinal carcinoma. The aim of the current study was to determine whether cathepsin D is a prognostic parameter for gastric carcinoma, and also to consider interaction with the urokinase‐plasminogen activator (uPA) system as an established risk factor for tumor‐associated proteolysis. METHODS In a consecutive prospective series of 203 gastric carcinoma patients, expression of cathepsin D in tumor cells was semiquantitatively analyzed with immunohistochemistry (scored 0‐3). Median follow‐up time was 31 months (range, 9‐56 months). Kaplan‐Meier (log rank) and multivariate Cox analyses were used to analyze survival. RESULTS Kaplan‐Meier analysis (log rank statistics) revealed significant association of increasing cathepsin D detection with poorer disease free survival ( P = 0.0042) and poorer overall survival ( P = 0.0018) of curatively resected patients. Overall survival of all patients was not significantly correlated. Multivariate analysis of established risk factors for gastric carcinoma, including the uPA system, identified cathepsin D as a new and independent prognostic parameter for disease free survival ( P = 0.020; relative risk, 2.98; 95% confidence interval, 1.28‐6.91). Plasminogen activator inhibitor type‐1 as a representative of the uPA system was confirmed as a strong independent factor for disease free and overall survival. Chi‐square analysis showed significant correlation of higher cathepsin D levels with Laurén's diffuse‐type carcinomas and strong evidence of uPA receptor in tumor cells. However, a subgroup analysis performed according to Laurén's classification revealed a univariate prognostic impact of cathepsin D on both diffuse and intestinal types without independent value. For patients with high levels of uPA receptor (scores of 2 and 3, n = 132), a highly significant association of increasing evidence of cathepsin D with disease free survival ( P < 0.0001) and overall survival ( P < 0.0001) was observed for curatively resected patients. Significant association with survival was also observed for all patients ( P = 0.0407). CONCLUSIONS Cathepsin D is a new functional prognostic parameter for gastric carcinoma patients with independent value for disease free survival. Moreover, this study indicates that consideration of more than one tumor‐associated protease could lead to a more individualized estimation of risk for carcinoma patients. Cancer 1997; 80:179‐87. © 1997 American Cancer Society.